McLeod Syndrome

Abstract

Neuroacanthocytosis (NA) syndromes are genetically defined neurodegenerative disorders characterized by the association of red blood cell acanthocytosis and progressive striatal neurodegeneration. The so-called core NA syndromes include autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. These two disorders have a Huntington disease-like phenotype consisting of a hyperkinetic, mostly choreatic, movement disorders, psychiatric manifestations, and cognitive decline with a relentlessly progressive course over several decades. In addition, they may have multisystem involvement including motor-dominant axonal neuropathy, myopathy, and cardiomyopathy. McLeod syndrome (MLS) is exceptionally rare with an estimated prevalence of less than 1–5 per 1,000,000 inhabitants. It is caused by mutations in the XK gene. Although the mechanism by which these mutations cause striatal neurodegeneration is not known, the association of the acanthocytic membrane abnormality with selective striatal degeneration suggests a common pathogenetic pathway. Useful diagnostic laboratory tests, besides blood smears to detect acanthocytosis, encompass determination of serum creatine kinase, since virtually all patients with McLeod syndrome reported to date have elevated levels. Cerebral magnetic resonance imaging may demonstrate striatal atrophy. Kell and Kx blood group antigens are reduced or absent, thus delivering an accurate diagnosis of McLeod syndrome, and identification of a distinct mutation in the XK gene is confirmatory. The course of McLeod syndrome is relentlessly progressive, and there is no curative therapy known yet. However, regular cardiologic studies and avoidance of transfusion complications are mandatory. The hyperkinetic movement disorder may be treated as in Huntington disease. Other symptoms including psychiatric manifestations should be managed in a symptom-oriented manner.